Electrochemical synthesis of cyclopropane ring compounds



United States Patent 3,321,387 ELECTRGCHEIWICAL SYNTHESIS OF CYCLO- PRGPANE RING CUB POUNDS William J. Koch], Jr., Yardley, Pa., assignor to Mobil Oil Corporation, a corporation of New York No Drawing. Filed July 25, 1963, Ser. No. 297,661 12 Claims. (Cl. 204-72) This invention relates to the preparation of cyclopropane ring compounds, including cyclopropane and substituted cyclopropanes, and particularly to the electrochemical synthesis of such compounds from carboxylic acids. The invention provides a much simpler method for making these compounds than the conventional process of removing halogen from a 1,2-dihalopropane, and it is further advantageous in yielding a number of valuable by-products.

As is known, cyclopropane is used as an inhalation anesthetic, and it and its derivatives are further useful in chemical synthesis as alkylating agents.

Essentially the invention comprises electrolyzing an aqueous solution of an aliphatic carboxylic acid, such as n-butanoic acid, 2-methylbutanoic acid, 3-methylbutanoic acid, n-pentanoic acid, and higher acids, by passing current from an anode to a cathode immersed in the solution to produce the cyclopropane n'ng compound at the anode, and recovering the same. The product is thus the result of an anodic oxidation of the carboxylic acid.

Considering the invention in greater detail, the aqueous solution that is electrolyzed may comprise broadly about 2 to 50%, preferably 5 to 20%, by weight of the free carboxylic acid together with a salt, preferably an alkali metal salt, of a carboxylic acid in an amount ranging from 2 or 3% to saturation, preferably from 5 to 20% by weight. The balance of the solution may comprise water. Preferably the salt is a salt of the same free acid. Suitable acids include those described, which comprise a preferred group, of which butanoic acid yields cyclopropane while each of the C-5 acids yields methylcyclopropane. Other acids are the C-6 acids like n-hexanoic, Z-methylpentanoic, 3-methylpentanoic, Z-ethylbutanoic, 4-methylpentanoic, and 2,3-dimethylbutanoic, which are useful to produce ethyl-substituted and 1,1- and 1,2-dimethyl-substituted derivatives. Higher acids like the C-7 acids, particularly the 2-, 3-, and 4-rnethylhexanoic acids, may lead to cyclopropane ring compounds having two alkyl substituents, i.e., methyl and ethyl, either on different carbons or on the same carbon, and acids like n-heptanoic and S-methylhexanoic may yield a propylsubstituted compound.

Other useful acids are the C-8, C-9, and C-l0 acids, and also including C-11 to C-14, or to C-16 or C-l8 acids, although their solubility becomes progressively lower as the molecular weight increases. In these instances, use of larger quantities of the above-noted salts tends to increase the solubility.

Generally speaking, the starting acid has at least 4 carbon atoms and the alpha carbon atom thereof has connected to it at least one group containing 2 or more carbons, such as ethyl, propyl, isopropyl, etc.

It will be understood that the presence of excess acid in the solution, even though it is undissolved therein, is permissible. It simply remains until the dissolved acid is electrolyzed or used up in the electrolyzing process, at which time it dissolves to replace the electrolyzed acid and is itself used up. It is also contemplated that the process may be continuously carried out, with acid being continuously introduced to the solution at a rate equal to, oreven slightly greater than, the rate at which it is electrochemically reacted.

It may be noted that the carboxylic acid salt may be added per se to the solution or formed in situ as by addition of a base like KOH or NaOH and reaction of the latter with part of the free carboxylic acid.

The pH of the electrolyte solution may initially be on the acid or alkaline side, or neutral, but preferably is on the acid side, and suitably may range from a pH of 5 to 7, more broadly from 3 to 7. When working on the acid side, it is convenient in batch processes to electrolyze the solution until a pH of 7 is reached, and then to collect products or replenish the solution. On the alkaline side the pH may range from 7 to 8 or 9.

The preferred anodes are of carbon, particularly graph ite, but may be of other inert materials like gold, nickel, brown lead oxide, etc. The cathode may be carbon or graphite or any inert metal such as copper, stainless steel, platinum, silver, nickel, lead, etc. Forms of the electrodes are conventional.

The current density may vary from 0.01 to 0.5, preferably from 0.04 to 0.2, amps/sq. cm. of anode area. Applied voltage is supplied by any suitable D.C. source. Room temperatures are preferred, although the temperature may range up to the boiling point of the solution and down close to the freezing point. The current efliciencies obtained may run about 40% and up, and in the case of n-butanoic acid may range up to If desired, a diaphragm of conventional material may be used to separate the cathode from the anode in order to prevent possible reaction of the products formed at one electnode with those at the other. Agitation is desirable although not necessary.

As indicated, the cyclopropane ring compound is formed at the anode by anodic oxidation. Normally gaseous compounds such as cyclopropane (B. 34 C.) and methylcyclopropane (B. 5 C.) may be recovered by collecting the gas, as by means of conventional water displacement methods and equipment. The anolyte may also be distilled to recover normally gaseous compounds and also lower boiling compounds, such as 1,1-dimethylcyclopropane (B. 21 C.). Higher boiling compounds may be recovered by conventional fractionation, or by extraction with a conventional solvent such as ether.

The preferred carbon anodes are made from graphite. Particularly good results are obtainable from the following illustrative materials:

TABLE A.ANODE CARBON Apparent Real Pore Identity Density, Density, Volume,

g./cc. g./cc. cc./g.

The invention may be illustrated by the following examples.

Example 1 A solution of 60 g. of potassium hydroxide and 250 ml. of n-butanoic acid in 250 ml. of Water was electrolyzed in an electrolytic cell at a temperature of 21 to 26 C., using a current of 4.0:02 amp. for 8 hours at 3 to 8 volts. The current density was 0.047 amp./ sq. cm. As the electrolysis proceeded, the applied voltage was increased within the foregoing range to maintain a constant current, and consequently the temperature also increased. The power supply was a variable transformer and rectifier. The cell was a closed glass vessel of 1 liter capacity equipped with a stirrer, thermometer, reflux condenser, and an electrode assembly, all disposed in a cooling bath. The electrode assembly consisted of four 1 x 32 x mm. copper plates and three 6.5 x 32 x 115 mm. carbon blocks which were stacked alternately and held 4 mm. apart by insulating spacers. The carbon blocks were made from KC graphite, note Table A, and were connected together as the anode, and the copper as the cathode. The electrode assembly was immersed in the electrolyte a depth of 4.5 cm., and the working area of the anode was 86 sq. cm.

The off-gas from the cell passed into the condenser, and non-condensable gas was collected in a conventional gas sampling bottle in which the gas flowing through the bottle displaced the air therein. The gas was sampled periodically and analyzed by vapor phase chromatography and mass spectrometry. The average composition of the gas in four samples was:

TABLE 1 Compound: Mole percent Hydrogen 36 Propylene 17 20 Cyclopropane 9 Carbon monoxide 2.2 Carbon dioxide 35 Small amounts of propane and butane were also found. The yield of cyclopropane based on the electricity consumed was of theoretical.

Example 2 A solution of 15 g. potassium hydroxide, 65 ml. n-b-utan'oic acid, and 65 ml. water was electrolyzed in a cell at 20 to 23 C., using a current of 0.8 amp. for 5% hours at 3 to 10 volts. The current density was 0.053 amp/sq. cm. This cell consisted of a closed cylindrical glass vessel .5 .0 cm. in diameter and 15 cm. in height fitted with a reflux condenser and a thermometer. The cathode was a copper cylinder 3.0 cm. in diameter and 5.0 cm. in height which was concentric with an anode comprising a 0.8 cm. diameter carbon welding rod of high density. The anode was immersed a depth of 6.0 cm. and had a working area of 15 sq. cm.

The off-gas was sampled and analyzed as in Example 1, and had the composition:

TABLE 2 Mole percent Reaction time elapsed when sample taken Hydrogen Propene Cyclopro- Carbon pane Dioxide 38. 14.9 5. 9 38. 5 45. 7 12.4 4.2 35.8 260 min 55.0 6. 9 2. 5 32.0

Example 3 Using the same cell as in Example 1, and the same cathode, but with a carbon anode identified as TPL, a solution of 10 g. sodium hydroxide, 100 ml. n-butanoic acid, and 400 ml. water was electrolyzed at a current density of 0.034 amp/sq. cm. at 2032 C. The actual current was 4.0 amps. at 4-15 volts. At the end of two hours of electrolysis, 35 grams of sodium sulphate were added and electrolysis continued at 22 C. using 4.0 amps. at 5 volts. After two hours, grams of sodium bicarbonate were added to give the solution a pH of 8 (its initial pH was on the acid side) and electrolysis continued at 4.0 amps. and 5 volts and a temperature of 22 C. At the end of two hours the experiment was discontinued. During the course of the experiment, off-gas from the anode was collected and examined by mass spectrometry. The following results were obtained.

Based on electricity, the foregoing cyclopropane yields correspond to 21%, 14%, and 5%. As is apparent, the use of sulphate and bicarbonate anions results in decreased yields. The bicarbonate addition reduced the yield to about 25% of that from the initial solution.

Example 4 In a series of runs, identified as 432, 433, 434, 444, and 448 in Table 4 below, n-pentanoic acid was electrolyzed in the cell of Example 1 at a current density of 0.042 amp/sq. cm. In runs 432, 433, 434, and 444, the solution (solution B) comprised 70 ml. pentanoic acid, 14 g. potassium hydroxide, and 400 ml. water; the current was 18 ampere hours; the voltage ranged from 5 to 25 volts; and the temperature from 20 to 40 C. In run 448, the solution (solution C) comprised 70 ml. pentanoic acid, g. sodium bicarbonate, and 400 ml. water; the current was 18 ampere hours; and the voltage was maintained at 5 volts, the temperature rising from 20 to 21 C. Carbon anodes were used for all runs, the type being indicated in the table, and it may be noted that the KC anode carbon was heated at 900 C. in carbon dioxide before use. The initial pH of each solution is also given. The table gives analyses of the gas produced in each run. For each run, data are given for three gas samples removed at evenly spaced intervals over the reaction time. As is apparent, all butene isomers were produced, as well as methylcyclopropane. The gas mixtures also contained 0.5% to 1.5% cyclopropane, 0.5 to 7.6% Propene, 2 to 5% ethylene, 0.5 to 4.5% n-butane, and traces of methane, ethane, and C-5 and C-6 compounds. Based on electricity, the methylcyclopropane yields varied from about 4 to 6.5%. Butene-l yields varied from 24 to about 29%.

TABLE 4.C4 HYDROCARBONS FROM PENTANOIC ACID, MOLE PERCENT Run pH Anode 1-Butene Iso-Butene Trans-2- Cis-2-Bute11e Methyley- Butene clopropane 58. 3 3.0 19. 2 9. 5 8. 4 432 6 KC 49.8 3. 8 19. 7 12. 6 8. 6 59. 3 3. 6 17. 4 10. 8 8. 1 54. 3 4.1 18. 3 9. 9 10. 7 433. 6 KC 48. 1 4.1 19. 7 13. 5 9. 6 55.9 3. 5 19.1 10.7 8. 4 51. 7 3.8 20. 4 10.4 12. 4 434..- 6 TPL 49. 2 3. 6 19. 6 12. 4 12.9 52. 5 5. 2 17. 7 9. 8 10. 1 55. 7 1. 8 l9. 2 9. 6 12. 9 444 6 HPL 52. 2 2. 1 19. 3 12. 1 12. 4 55. 5 2. 8 17. 9 10.8 9. 8 63.0 14. 3 7. 4 14. 8 448..- 8 KC 55.1 20.0 12.0 10.8 54. 9 18. 7 11.9 12.2

Example 5 In two runs, identified in Table 5 below as 451 and 452, Z-methylbutanoic acid was electrolyzed in the cell of Example 1 at a current density of 0.042 amp/ sq. cm. In run 451, the solution was the same as solution B of Example 4 except that 2-methylbutanoic acid was used instead of n-pentanoic acid; the current passed through the solution was 18 ampere hours; the voltage ranged from 5 to 25 volts and the temperature from to 40 C. In run 452, the solution was the same as solution C of Example 4 except that Z-methyl-butanoic acid was used instead of n-pentanoic acid; the current was 18 ampere hours; the voltage was maintained at 5 volts, the temperature rising from 20 to 21 C. Carbon anodes were used of the type indicated. The initial pH of each solution is also given. For each run, data are given for two gas samples removed at evenly spaced intervals over the reaction time. All =butene isomers were produced, as well as methylcyclopropane. The gas mixtures also contained 0.4 to 1.4% n-butane, 0.5 to 0.7% isobutane, l to 3% ethylene, and traces of methane, ethane, propane, and C-5 and C6 compounds. Yields based on electricity ranged from about 1 to 2.5% for methylcyclopropane and about 11 to 28% for l-butene.

electricity basis, and in addition substantial yields of valuable by-products are obtainable.

While aqueous solutions of the electrolyte are preferred, it is possible to employ non-aqueous solutions. The usual objections to the latter is that they are poor conductors, but they do have an advantage in that the solubility, particularly of the higher carboxylic acids, may be increased if the latter are dissolved in a nonaqueous electrolyte, of which suitable examples include methanol, ethylene glycol, acetonitrile, dimethyl sulfoxide, etc.

It will be understood that the invention is capable of obvious variations without departing from its scope.

In the light of the foregoing descriptions, the following is claimed:

1. Method of electrochemically synthesizing a cyclopropane ring compound which comprises electrolyzing an aqueous solution of an aliphatic carboxylic acid selected from the group consisting of n-butanoic acid, 2- methylbutanoic acid, 3-methylbutanoic acid, and npentanoic acid by passing current from an anode to a cathode immersed in said solution at a current density of 0.01 to 0.5 amp/sq. cm. to produce at the anode a gaseous product containing said cyclopropane ring compound, and recovering the same.

TABLE 5 Run pH Anode l-Butene Iso-Butene Trans-2- Cis-2-Butene Methyley- Butene clopropane 51. 5 2. 2 27. 1 12. 7 4. 9 451m" 5 NC 60 i 25.5 2.6 gas 11.7 4.9 6 9. 1 14. 5 3. 8 452m" 8 NC 60 i 45.6 1.8 31.6 16.8 3. 5

Example 6 Three additional runs, identified as 456, 459, and 487 were made in which 3-methylbutanoic acid was electrolyzed in the cell of Example 1 at a current density of 0.042 amp/sq. cm. In run 456, the solution was the same as solution B of Example 4 except that 3-methylbutanoic acid was used instead of n-pentanoic acid. The current was 18 ampere hours, the voltage 5 to volts and the temperature 20 to C. In runs 459 and 487, the solution was the same as solution C of Example 4 except that 3-methylbutanoic acid was used instead of n-pentanoic acid; the current was 18 ampere hours, the voltage 5 volts, and the temperature 20 to 21 C. Table 6 gives the type of anode carbon, and the initial pH of each solution. Data are given for two gas samples removed at evenly spaced intervals over the reaction time. In addition to the products noted, the gas mixtures contained 0.2 to 0.8% n-butane, 0.8 to 6.2% isobutane, 1.7 to 3.6% propene, 1 to 3% ethylene, and traces of methane, ethane, propane, and C-5 and C-6 compounds. Electricity yields were about 2 to 4.9% for methylcyclopropane and about 8 to 17% for butene-l.

2. Method of electrochemically synthesizing cyclopropane which comprises electrolyzing an aqueous solution of n-butanoic acid containing an alkali metal salt of said acid by passing current from an anode to a cathode immersed in said solution at a current density of 0.01 to 0.5 amp/sq. cm. to produce at the anode said cyclopropane, and recovering the same.

3. Method of electrochemically synthesizing a methylsubstituted cyclopropane which comprises electrolyzing an aqueous solution of a pentanoic acid containing an alkali metal salt of said acid, said pentanoic acid being selected from the group consisting of n-pentanoic acid, 2methylbu-tanoic acid, and 3-methylbutanoic acid, said method including passing current from an anode to a cathode immersed in said solution at a current density of 0.01 to 0.5 amp./sq. cm. to produce at the anode said methyl-substituted cyclopropane, and recovering the same.

4. Method of claim 1 in which the electrolysis is carried out in the absence of inert anions.

5. Method of electrochemically synthesizing a cyclopropane ring compound which comprises passing current from an anode to a cathode immersed in a solution of an aliphatic carboxylic acid having at least 4 carbon atoms,

TABLE 6 Run pH Anode l-Butene Iso-Butene Trans-2- Cis-Z-Butene Methylcyclopropane r 28.8 28. o 18.5 9. 9 7. 9 6 NC gag 19.1 9.8 6.7 6. 17.0 10.3 8.5 8 NC 60 It will be apparent that the invention provides a convenient method for making cyclopropane and alkyl-substituted cyclopropanes starting from readily available carboxylic acids. The only chemicals required are the acids and acid salts, and the latter may be formed in situ from the acid and a conventional caustic. As demonstrated, yields of cyclic compound range up to 25%,

Po the alpha carbon atom in said acid being connected to at least one group having two or more carbon atoms, said solution also containing an alkali metal salt of a carboxylic acid, producing said cyclopropane ring compound at the anode, and recovering the same.

6. A method for preparing a cyclopropane ring compound comprising passing current from an anode to a cathode through an aqueous solution containingZ to 50% by weight of a free aliphatic carboxylic acid, at least 2% by weight of an alkali metal salt of a carboxylic acid, and the balance water, said free acid having at least 4 carbon atoms and the alpha carbon atom therein being connected to at least one group having tWo or more carbon atoms, said anode being of graphite, producing said cyclopropane ring compound at the anode, and recovering the same.

7. The method of claim 6 wherein the concentration of said acid salt ranges from 2% by weight of said solution to the saturation concentration thereof.

8. The method of claim 6 wherein the concentration of said free acid is 5 to 20% by weight of said solution and the concentration of said salt is 5 to 20% by weight of said solution. 7

9. The method of claim 6 wherein said free acid and the acid from which said salt is derived are the same.

10. The method of claim 6 wherein said cyclopropane ring compound is continuously removed from said solution and said free acid is continuously introduced thereto.

11. The method of claim 6 wherein a portion of said free acid is initially present in said solution in undissolved form and wherein said portion dissolves as free acid is electrochemically reacted.

12. The method of claim 6 wherein said graphite is characterized by having a real density of at least 2.0

g./cc. and a pore volume of less than 0.5 cc./ g.

References Cited by the Examiner UNITED STATES PATENTS 2,867,569 1/1959 Kronenthal 204-79 X JOHN H. MACK, Primary Examiner.

D. R. VALENTINE, Assistant Examiner. 

1. METHOD OF ELECTROCHEMICALLY SYNTHESIZING A CYCLOPROPANE RING COMPOUND WHICH CMPRISES ELECTROLYZING AN AQUEOUS SOLUTION OF AN ALIPHATIC CARBOXYLIC ACID SELECTED FROM THE GROUP CONSISTING OF N-BUTANOIC ACID, 2METHYLBUTANOIC ACID, 3-METHYLBUTANOIC ACID, AND NPENTANIC ACID BY PASSING CURRENT FROM AN ANODE TO A CATHODE IMMERSED IN SAID SOLUTION AT A CURRENT DENSITY OF 0.01 TO 0.5 AMP./SQ. CM. TO PRODUCE AT THE ANODE A GASEOUS PRODUCT CONTAINING SAID CYCLOPROPANE RING COMPOUND, AND RECOVERING THE SAME. 